Abi-Dargham A, Kegeles LS, Zea-Ponce Y, Mawlawi O, Martinez D, Mitropoulou V et al. Striatal amphetamine-induced dopamine release in patients with schizotypal personality disorder studied with single photon emission computed tomography and [ 123I] iodobenzamide. Biol Psychiatry 55: 1001-1006

Department of Psychiatry, Columbia University, and New York State Psychiatric Institute, New York, 10032, USA.
Biological Psychiatry (Impact Factor: 10.26). 06/2004; 55(10):1001-6. DOI: 10.1016/j.biopsych.2004.01.018
Source: PubMed


Previous imaging studies demonstrated that schizophrenia is associated with increased amphetamine-induced dopamine (DA) release in the striatum, most pronounced during episodes of illness exacerbation. Schizotypal personality disorder (SPD) is a schizophrenia spectrum disorder, genetically related to schizophrenia. The goal of this study was to investigate striatal DA function in patients with SPD.
In our study, 13 SPD patients and 13 matched healthy control subjects underwent single photon emission computed tomography (SPECT) scan during bolus plus constant infusion of the D2/3 radiotracer [123I]iodobenzamide (IBZM). Striatal specific to nonspecific equilibrium partition coefficient (V(3)") was measured at baseline and following amphetamine administration (.3 mg/kg).
No significant differences were observed in baseline V(3)" between groups. Amphetamine induced a larger decrease in [123I]IBZM V(3)" in SPD patients (-12 +/- 5%) compared with control subjects (-7 +/- 5%, p =.03).
The reduction in [123I]IBZM V(3)" induced by amphetamine in SPD was similar to that observed in remitted schizophrenia patients (-10 +/- 9%, n = 17), but significantly lower than that observed during illness exacerbation (-24 +/- 13%, n = 17). This suggests that DA dysregulation in schizophrenia spectrum disorders might have a trait component, present in remitted patients with schizophrenia and in SPD, and a state component, associated with psychotic exacerbations but not SPD.

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Available from: Lawrence S Kegeles, Jul 18, 2014
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    • "A recent single-photon emission computed tomography (SPECT) investigation revealed that the availability of striatal D2 receptors is associated with schizotypal features in healthy volunteers (Chen et al., 2012). Finally, another study in patients with schizotypal personality disorder (SPD) indicated exaggerated dopamine release in the striatum following d-amphetamine challenge (Abi-Dargham et al., 2004). However, more investigation of the function of brain networks is needed to map schizotypy in healthy individuals onto the Gaussian distribution of schizophrenia risk. "
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    ABSTRACT: "Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.
    Frontiers in Behavioral Neuroscience 07/2014; 8(235):eCollection2014. DOI:10.3389/fnbeh.2014.00235 · 3.27 Impact Factor
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    • "Imaging studies have shown that patients with schizophrenia, both in the acute phase and in remission, show amphetamine-induced reductions in D2 and D3 dopamine receptor binding potential in the striatum (177, 178). Similar findings were obtained in patients with schizotypal personality disorder (179). Importantly, a relationship between striatal dopamine release after amphetamine and SPQ schizotypy was observed in a sample of non-clinical volunteers (180), providing support for a shared dopaminergic dysfunction in schizotypy and schizophrenia. "
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    ABSTRACT: Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function, and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia. Evidence was corroborated that significant overlap exists between the two, covering the behavioral brain structural and functional as well molecular levels. In particular, several studies showed that individuals with high levels of schizotypal traits exhibit alterations in neurocognitive task performance and underlying brain function similar to the deficits seen in patients with schizophrenia. Studies of brain structure have shown both volume reductions and increase in schizotypy, pointing to schizophrenia-like deficits as well as possible protective or compensatory mechanisms. Experimental pharmacological studies have shown that high levels of schizotypy are associated with (i) enhanced dopaminergic response in striatum following administration of amphetamine and (ii) improvement of cognitive performance following administration of antipsychotic compounds. Together, this body of work suggests that schizotypy shows overlap with schizophrenia across multiple behavioral and neurobiological domains, suggesting that the study of schizotypal traits may be useful in improving our understanding of the etiology of schizophrenia.
    Frontiers in Psychiatry 02/2014; 5:18. DOI:10.3389/fpsyt.2014.00018
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    • "Patients with schizophrenia increase their baseline occupancy of D 2 receptors by DA and the availability of their D 2 receptors is higher than that of controls' D 2 receptors after DA depletion (Abi-Dargham et al., 2000). The hyperfunction of the striatal DA system has been previously suggested to be one of the key pathophysiological mechanisms in schizophrenic psychosis (Snyder, 1976; Davis et al., 1991; Abi-Dargham et al., 2004; Howes et al., 2009). Positive symptoms, which may be induced by the increase in synaptic DA concentration in the striatum (Breier et al., 1997; de Haan et al., 2004; Yang et al., 2004; Buchsbaum et al., 2006; Schmitt et al., 2008), play an important part in the diagnosis of schizophrenia. "
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    ABSTRACT: Individuals with schizotypal features exhibit cognitive, perceptual and social deficits that are similar to but less prominent than those seen in patients with schizophrenia. Dopaminergic hyperactivity in the striatum has been related to the positive symptoms of schizophrenia, and brain-imaging studies of dopamine uptake in the striatum are thought to be linked to the pathophysiological mechanisms underlying schizophrenia. The aim of this study was to investigate whether the increased availability of striatal dopamine (DA) D(2/3) receptors is related to elevated levels of schizotypal features in healthy individuals. The Schizotypal Personality Questionnaire (SPQ) was administered to 55 healthy volunteers. The availability of their striatal DA D(2/3) receptors was analysed using [(123)I] iodobenzamide single photon emission computed tomography (SPECT). Although the SPQ total scores showed no correlation with the availability of total (left and right) striatal DA D(2) receptors, the SPQ disorganised subscale scores were positively correlated with the availability of right striatal DA D(2/3) receptors. Our findings demonstrated that the availability of striatal DA D(2/3) receptors may be associated with schizotypal features in healthy volunteers.
    Psychiatry Research 03/2012; 201(3):218-21. DOI:10.1016/j.pscychresns.2011.07.003 · 2.47 Impact Factor
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